Mucosal Inflammation Program, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
J Immunol. 2011 Oct 1;187(7):3475-81. doi: 10.4049/jimmunol.1100150.
Mucosal surfaces function as selectively permeable barriers between the host and the outside world. Given their close proximity to microbial Ags, mucosal surfaces have evolved sophisticated mechanisms for maintaining homeostasis and preventing excessive acute inflammatory reactions. The role attributed to epithelial cells was historically limited to serving as a selective barrier; in recent years, numerous findings implicate an active role of the epithelium with proresolving mediators in the maintenance of immunological equilibrium. In this brief review, we highlight new evidence that the epithelium actively contributes to coordination and resolution of inflammation, principally through the generation of anti-inflammatory and proresolution lipid mediators. These autacoids, derived from ω-6 and ω-3 polyunsaturated fatty acids, are implicated in the initiation, progression, and resolution of acute inflammation and display specific, epithelial-directed actions focused on mucosal homeostasis. We also summarize present knowledge of mechanisms for resolution via regulation of epithelial-derived antimicrobial peptides in response to proresolving lipid mediators.
黏膜表面作为宿主与外界之间具有选择性渗透性的屏障发挥作用。鉴于它们与微生物抗原的密切接近,黏膜表面已经进化出了复杂的机制来维持体内平衡和防止过度的急性炎症反应。历史上,上皮细胞的作用仅限于作为选择性屏障;近年来,许多研究结果表明,上皮细胞通过产生具有促解决介质的上皮细胞在维持免疫平衡中发挥着积极作用。在这篇简短的综述中,我们强调了新的证据,表明上皮细胞通过产生抗炎和促解决脂质介质,积极参与炎症的协调和解决。这些自分泌物质来源于ω-6 和 ω-3 多不饱和脂肪酸,与急性炎症的发生、发展和解决有关,并表现出针对黏膜稳态的特定的、上皮细胞定向的作用。我们还总结了目前通过对促解决脂质介质的反应来调节上皮细胞衍生的抗菌肽以实现解决的机制的知识。